Tim-3 is a member of the T-cell immunoglobulin domain and Mucin domain protein (Tim) family in structure. Tim family is widely involved in immunoregulation processes of the body, and thus people paid more attention to the function of this family. Tim-3 is specifically expressed on the surface of activated Th1 and Th17 effector cells, but not on Th2 cells. It is known in the art that Galectin-9 (Gal-9) is the natural ligand for Tim-3, and this molecule is widely expressed in peripheral immune system. After Tim-3 and Gal-9 are combined, a series of signal pathways can be activated so as to inhibit the activation of immunocytes, including T-cells and innate immunocytes such as macrophage etc. It was indicated in some studies that the high expression of Tim-3 on immunocytes is closely related to the immune dysfunction in patients with tumor and chronic viral infection. It was also indicated that such means capable of blocking the combination of Tim-3 and Gal-9 can prevent the Th1 and Th17 cells from dying, enhance the activities of T-effector cells, and recover the immune functions.
In one aspect, in some autoimmune diseases like systemic lupus erythematosus (SLE) and asthma etc., the increased expression of Gal-9 or Tim-3 will inhibit the functions of Th1 cells, which in turn breaks the immunologic balance of the body, and results in the increased activity of pathological Th2 cells and therefore onset of diseases. Under the circumstances, such means capable of blocking the combination of Tim-3/Gal-9 can promote the recovery of immunologic balance of the body and alleviate the progression of diseases. In another aspect, in some autoimmune diseases like inflammatory bowel disease and type I diabetes mellitus, some studies showed that blocking the activities of Tim-3 can enhance the functions of Th1 effector cells in the body, which further increases the autoimmune damages. The results also indicate that Tim-3 plays an important role in maintaining the immunologic balance of the body.
It is shown in the above studies that Tim-3 pathway has important immune regulatory functions, and abnormal expression of Tim-3 is closely related to the onsets and progressions of many kinds of diseases. However, there is no blocking agent for Tim-3 signal pathway with good effects so far. Accordingly, to better study the pathogenesis of some diseases and improve the diagnosis and treatment thereof, it is important to develop a blocking agent for Tim-3 signal pathway with high specificity and good blocking effect.